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Immediate implantation of ultrafine fiber slow-release system based on cell electrospinning to induce osteogenesis of mesenchymal stem cells

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Regenerative Biomaterials 2024年第2期3卷 76-87页

作者： Tao Lu Long Yang Zhuoyang Li Yin Liu Shun'en Xu Chuan Ye department of Orthopaedics The Affliated Hospital of Guizhou Medical UniversityGuiyang 550004China department of Orthopaedics The First People's Hospital of GuiyangGuiyang 550004China center for Tissue Engineering and Stem Cell Research Guizhou Medical UniversityGuiyang 550004China department of Otolaryngology Head and Neck Surgery Xinqiao HospitalArmy Medical University(Third Military Medical University)Chongqing 400037China department of dental implant Stomatological Hospital of GuiyangGuiyang 550000China

This study presents the development and evaluation of a poly(3-hydroxybutyrate-co-4-hydroxybutyrate)(P34HB)ultrafine fiber slow-release system for in vivo osteogenic induction of human umbilical cord mesenchymal stem cells(HUCMSCs).Utilizing dual-nozzle and cell electrospinning techniques,the system encapsulates L-ascorbic acid-2-phosphate magnesium(AsP),βB-glycerophosphate sodium and dexamethasone(DEX)within the'fbers,ensuring sustained osteogenic differentiation.The scaffold's morphology,characterization,hydrophilicity,mechanical properties and cellular behavior were examined.Immediate subcutaneous implantation in rabbits was con-ducted to observe its ectopic osteogenic induction effect.Successfully fabricated P34HB ultrafine fiber slow-release sys-tem.Charact ization med.theuniform distribution of HUCMSCs and inducing components within the scaffold,with no chemical reactions affecting the active components.In vitro tests showcased a prolonged release of DEX and ASP,while biocompatibility assays highlighted the scaffold's suitability for cellular growth.Alizarin Red,type I collagen,and osteopontin(OPN)staining verifed the scaffold's potent osteogenic induction effect on HUCMsCs.Notably,immediate implantation into New Zealand White rabbits led to significant new bone formation within 8 weeks.These findings underscore the system's potential for immediate in vivo implantation without prior in vitro induction,marking a promising advancement in bone tissue engineering.

关键词： bone tissue engineering cell electrospinning in vivo induction immediate implantation biomaterials

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Bioinspired polysaccharide-based nanocomposite membranes with robust wet mechanical properties for guided bone regeneration

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National Science Review 2024年第3期11卷 215-226页

作者： Jian-Hong Xiao Zhen-Bang Zhang JiaHao Li Si-Ming Chen Huai-Ling Gao YinXiu Liao Lu Chen ZiShuo Wang YiFan Lu YuanZhen Hou HengAn Wu DuoHong Zou Shu-Hong Yu department of Chemistry New Cornerstone Science Laboratory Institute of Biomimetic Materials&Chemistry Anhui Engineering Laboratory of Biomimetic MaterialsDivision of Nanomaterials&Chemistry Hefei National Research Center for Physical Sciences at the Microscale University of Science and Technology of China department of dental implant center Stomatologic Hospital and College Key Laboratory of Oral Diseases Research of Anhui Province Anhui Medical University CAS Key Laboratory of Mechanical Behavior and Design of Materials Department of Modern Mechanics CAS Center for Excellence in Complex System Mechanics University of Science and Technology of China department of Oral Surgery College of Stomatology National Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology Shanghai Research Institute of Stomatology Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Institute of Innovative Materials(I2M) Department of Chemistry Department of Materials Science and Engineering Southern University of Science and Technology

Polysaccharide-based membranes with excellent mechanical properties are highly desired. However, severe mechanical deterioration under wet conditions limits their biomedical applications. Here, inspired by the structural heterogeneity of strong yet hydrated biological materials, we propose a strategy based on heterogeneous crosslink-and-hydration（HCH） of a molecule/nano dual-scale network to fabricate polysaccharide-based nanocomposites with robust wet mechanical properties. The heterogeneity lies in that the crosslink-and-hydration occurs in the molecule-network while the stress-bearing nanofiber-network remains unaffected. As one demonstration, a membrane assembled by bacterial cellulose nanofiber-network and Ca2+-crosslinked and hydrated sodium alginate molecule-network is designed. Studies show that the crosslinked-and-hydrated molecule-network restricts water invasion and boosts stress transfer of the nanofiber-network by serving as interfibrous bridge. Overall, the molecule-network makes the membrane hydrated and flexible; the nanofiber-network as stress-bearing component provides strength and toughness.The HCH dual-scale network featuring a cooperative effect stimulates the design of advanced biomaterials applied under wet conditions such as guided bone regeneration membranes.

关键词： bioinspiration heterogeneous crosslink-and-hydration dual-scale network nanocomposite membrane wet mechanical properties guided bone regeneration

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Metabolic memory:mechanisms and diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1086-1114页

作者： Hao Dong Yuezhang Sun Lulingxiao Nie Aimin Cui Pengfei Zhao Wai Keung Leung Qi Wang State Key Laboratory of Oral Diseases&National center for Stomatology&National Clinical Research center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina department of Prosthodontics West China Hospital of StomatologySichuan UniversityChengduChina Periodontology and implant Dentistry Division Faculty of DentistryThe University of Hong KongHong KongChina

Metabolic diseases and their complications impose health and economic burdens worldwide.Evidence from past experimental studies and clinical trials suggests our body may have the ability to remember the past metabolic environment,such as hyperglycemia or hyperlipidemia,thus leading to chronic inflammatory disorders and other diseases even after the elimination of these metabolic environments.The long-term effects of that aberrant metabolism on the body have been summarized as metabolic memory and are found to assume a crucial role in states of health and disease.Multiple molecular mechanisms collectively participate in metabolic memory management,resulting in different cellular alterations as well as tissue and organ dysfunctions,culminating in disease progression and even affecting offspring.The elucidation and expansion of the concept of metabolic memory provides more comprehensive insight into pathogenic mechanisms underlying metabolic diseases and complications and promises to be a new target in disease detection and management.Here,we retrace the history of relevant research on metabolic memory and summarize its salient characteristics.We provide a detailed discussion of the mechanisms by which metabolic memory may be involved in disease development at molecular,cellular,and organ levels,with emphasis on the impact of epigenetic modulations.Finally,we present some of the pivotal findings arguing in favor of targeting metabolic memory to develop therapeutic strategies for metabolic diseases and provide the latest reflections on the consequences of metabolic memory as well as their implications for human health and diseases.

关键词： diseases metabolism alterations

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3D-printed Mg-1Ca/polycaprolactone composite scaffolds with promoted bone regeneration

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Journal of Magnesium and Alloys 2024年第3期12卷 966-979页

作者： Xiao Zhao Siyi Wang Feilong Wang Yuan Zhu Ranli Gu Fan Yang Yongxiang Xu Dandan Xia Yunsong Liu department of Prosthodontics Peking University School and Hospital of StomatologyBeijing 100081China National center of Stomatology National Engineering Laboratory for Digital and Material Technology of StomatologyNational Clinical Research Center for Oral DiseasesBeijing Key Laboratory of Digital StomatologyResearch Center of Engineering and Technology for Computerized Dentistry Ministry of HealthNMPA Key Laboratory for Dental MaterialsBeijing 100081China department of dental Materials Peking University School and Hospital of StomatologyBeijing 100081China

In bone tissue engineering,polycaprolactone(PCL)is a promising material with good biocompatibility,but its poor degradation rate,mechanical strength,and osteogenic properties limit its application.In this study,we developed an Mg-1Ca/polycaprolactone(Mg-1Ca/PCL)composite scaffolds to overcome these limitations.We used a melt blending method to prepare Mg-1Ca/PCL composites with Mg-1Ca alloy powder mass ratios of 5,10,and 20 wt%.Porous scaffolds with controlled macro-and microstructure were printed using the fused deposition modeling method.We explored the mechanical strength,biocompatibility,osteogenesis performance,and molecular mechanism of the Mg-1Ca/PCL composites.The 5 and 10 wt%Mg-1Ca/PCL composites were found to have good biocompatibility.Moreover,they promoted the mechanical strength,proliferation,adhesion,and osteogenic differentiation of human bone marrow stem cells(hBMSCs)of pure PCL.In vitro degradation experiments revealed that the composite material stably released Mg_(2)+ions for a long period;it formed an apatite layer on the surface of the scaffold that facilitated cell adhesion and growth.Microcomputed tomography and histological analysis showed that both 5 and 10 wt%Mg-1Ca/PCL composite scaffolds promoted bone regeneration bone defects.Our results indicated that the Wnt/β-catenin pathway was involved in the osteogenic effect.Therefore,Mg-1Ca/PCL composite scaffolds are expected to be a promising bone regeneration material for clinical application.Statement of significance:Bone tissue engineering scaffolds have promising applications in the regeneration of critical-sized bone defects.However,there remain many limitations in the materials and manufacturing methods used to fabricate scaffolds.This study shows that the developed Ma-1Ca/PCL composites provides scaffolds with suitable degradation rates and enhanced boneformation capabilities.Furthermore,the fused deposition modeling method allows precise control of the macroscopic morphology and microscopic porosity of the scaffold.The obtained porou

关键词： 3D printing Bone tissue engineering Magnesium Osteogenic Polycaprolactone Scaffold.

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Nanozyme‑Engineered Hydrogels for Anti‑Inflammation and Skin Regeneration

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Nano-Micro Letters 2024年第6期16卷 127-179页

作者： Amal George Kurian Rajendra K.Singh Varsha Sagar Jung‑Hwan Lee Hae‑Won Kim Institute of Tissue Regeneration Engineering(ITREN) Dankook UniversityCheonan 31116Republic of Korea department of Nanobiomedical Science&BK21 NBM Global Research center for Regenerative Medicine Dankook UniversityCheonan 31116Republic of Korea department of Biomaterials Science School of DentistryDankook UniversityCheonan 31116Republic of Korea UCL Eastman‑Korea dental Medicine Innovation Centre Dankook UniversityCheonan 31116Republic of Korea Cell and Matter Institute Dankook UniversityCheonan 31116Republic of Korea Mechanobiology dental Medicine Research center Dankook UniversityCheonan 31116Republic of Korea

Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-inflammatory drugs,are limited in efficacy and associated with adverse effects.Recently,nanozyme(NZ)-based hydrogels have shown great promise in addressing these challenges.NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels.The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation.This review highlights the current state of the art in NZ-engineered hydrogels(NZ@hydrogels)for anti-inflammatory and skin regeneration applications.It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness.Additionally,the challenges and future directions in this ground,particularly their clinical translation,are addressed.The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels,offering new possibilities for targeted and personalized skin-care therapies.

关键词： Nanozymes Hydrogels ROS scavenging Anti-inflammation Skin regeneration

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Deficiency of Trp53 and Rb1 in myeloid cell lineage spontaneously develops acute myeloid leukemia in a mouse model

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Genes & Diseases 2024年第1期11卷 4-6页

作者： Yang Li Shu-ting Yang Shuying Yang department of Basic&Translational Sciences School of Dental MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA department of Orthopaedic Surgery School of MedicineJohns Hopkins University BaltimoreMD 21205USA center for Innovation&Precision Dentistry School of Dental MedicineSchool of Engineering and Applied SciencesUniversity of PennsylvaniaPhiladelphiaPA 19104USA The Penn center for Musculoskeletal Disorders School of MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

Acute myeloid leukemia(AML)is a rapidly lethal blood cancer characterized by aberrant proliferation and differentiation of myeloid progenitors in the hematopoietic tissue.In recent decades,AML patients are significantly increased.In 2019 alone,21,450 new AML cases were diagnosed in the United States,with an estimated 10,920 deaths due to AML.What’s worse,AML occurs with an increasing incidence with advanced age,and the survival rate remains dismal with a median overall survival of only 5e10 months.Notwithstanding great advances in allogenic transplant and chemotherapy,the therapeutic outcomes are unfavorable due to the disease relapse and mortality rates.More importantly,the development of more specific and effective therapies was hampered in part by the lack of proper animal models for AML.Thus,management and elucidation of the pathological mechanism of AML remain an ongoing challenge,and the development of effective AML mouse models and treatment options are urgently needed.

关键词： myeloid Acute leukemia

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Highly Aligned Ternary Nanofiber Matrices Loaded with MXene Expedite Regeneration of Volumetric Muscle Loss

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Nano-Micro Letters 2024年第4期16卷 269-292页

作者： Moon Sung Kang Yeuni Yu Rowoon Park Hye Jin Heo Seok Hyun Lee Suck Won Hong Yun Hak Kim Dong‑Wook Han department of Cogno‑Mechatronics Engineering College of Nanoscience and NanotechnologyPusan National UniversityBusan 46241Republic of Korea Medical Research Institute School of MedicinePusan National UniversityYangsan 50612Republic of Korea department of Anatomy School of MedicinePusan National UniversityYangsan 50612Republic of Korea Engineering Research center for Color‑Modulated Extra‑Sensory Perception Technology Pusan National UniversityBusan 46241Republic of Korea department of Biomedical Informatics School of MedicinePusan National UniversityYangsan 50612Republic of Korea Periodontal Disease Signaling Network Research center and dental and Life Science Institute School of DentistryPusan National UniversityYangsan 50612Republic of Korea BIO‑IT Fusion Technology Research Institute Pusan National UniversityBusan 46241Republic of Korea Present Address:Osstem implant Inc. Seoul 07789Republic of Korea

Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient bioactivities.To overcome these limitations,tissue-engineered scaffolds have emerged as a promising alternative.In this study,we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone)integrated with collagen and Ti_(3)C_(2)T_(x)MXene nanoparticles(NPs)(PCM matrices),and explored their myogenic potential for skeletal muscle tissue regeneration.The PCM matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and hydrophilicity.In vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 myoblasts.Moreover,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML injury.Mechanistic insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices,leading to elevated intracellular Ca^(2+)levels in myoblasts through the activation of inducible nitric oxide synthase(i NOS)and serum/glucocorticoid regulated kinase 1(SGK1),ultimately promoting myogenic differentiation via the m TOR-AKT pathway.Additionally,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast maturation.These findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.

关键词： Ti_(3)C_(2)T_(x)MXene nanoparticle Ternary nanofibrous matrices Myogenesis Regeneration of volumetric muscle loss Next generation sequencing

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Integrated ribosome and proteome analyses reveal insights into sevoflurane-induced long-term social behavior and cognitive dysfunctions through ADNP inhibition in neonatal mice

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Zoological Research 2024年第3期45卷 663-678页

作者： Li-Rong Liang Bing Liu Shu-Hui Cao You-Yi Zhao Tian Zeng Mei-Ting Zhai Ze Fan Dan-Yi He San-Xin Ma Xiao-Tong Shi Yao Zhang Hui Zhang State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Engineering Research Center for Dental Materials and Advanced ManufactureDepartment of AnesthesiologySchool of StomatologyAir Force Medical UniversityXi’anShaanxi 710032China department of Anesthesiology 986th Air Force HospitalAir Force Medical UniversityXi’anShaanxi 710032China

A growing number of studies have demonstrated that repeated exposure to sevoflurane during development results in persistent social abnormalities and cognitive impairment.Davunetide,an active fragment of the activity-dependent neuroprotective protein(ADNP),has been implicated in social and cognitive protection.However,the potential of davunetide to attenuate social deficits following sevoflurane exposure and the underlying developmental mechanisms remain poorly understood.In this study,ribosome and proteome profiles were analyzed to investigate the molecular basis of sevoflurane-induced social deficits in neonatal mice.The neuropathological basis was also explored using Golgi staining,morphological analysis,western blotting,electrophysiological analysis,and behavioral analysis.Results indicated that ADNP was significantly down-regulated following developmental exposure to sevoflurane.In adulthood,anterior cingulate cortex(ACC)neurons exposed to sevoflurane exhibited a decrease in dendrite number,total dendrite length,and spine density.Furthermore,the expression levels of Homer,PSD95,synaptophysin,and vglut2 were significantly reduced in the sevoflurane group.Patch-clamp recordings indicated reductions in both the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSCs).Notably,davunetide significantly ameliorated the synaptic defects,social behavior deficits,and cognitive impairments induced by sevoflurane.Mechanistic analysis revealed that loss of ADNP led to dysregulation of Ca^(2+)activity via the Wnt/β-catenin signaling,resulting in decreased expression of synaptic proteins.Suppression of Wnt signaling was restored in the davunetide-treated group.Thus,ADNP was identified as a promising therapeutic target for the prevention and treatment of neurodevelopmental toxicity caused by general anesthetics.This study provides important insights into the mechanisms underlying social and cognitive disturbances caused by sevoflurane exposure in neonatal mice and elucidates the regulatory pathways invo

关键词： Davunetide Sevoflurane Abnormal social behaviors ADNP Neurotoxicity

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Unraveling the role of METTL14 in metabolic dysfunction-associated fatty liver disease:insights and therapeutic implications

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1781-1783页

作者： So Jung Kim Jeongeun Hyun Institute of Tissue Regeneration Engineering(ITREN) Dankook UniversityCheonanRepublic of Korea department of Nanobiomedical Science and BK21 PLUS NBM Global Research center for Regenerative Medicine Dankook UniversityCheonanRepublic of Korea Mechanobiology dental Medicine Research center College of DentistryDankook UniversityCheonanRepublic of Korea

The recent article published in Signal Transduction and Targeted Therapy sheds light on the significance of N6-methyladenosine(m6A)methyltransferase-like protein METTL14 in mitigating the progression of metabolic dysfunction-associated fatty liver disease(MAFLD).1 In this study,Wang et al.elucidated the downregulation of METTL14 in hepatocytes from both MAFLD patients and high-fat diet(HFD)-induced MAFLD mouse models,underscoring its pivotal role in maintaining hepatic lipid and redox homeostasis in normal livers.

关键词： liver homeostasis al.

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The deterministic condition for the ground reaction force acting point on the combined knee valgus and tibial internal rotation moments in early phase of cutting maneuvers in female athletes

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Journal of Sport and Health Science 2024年第3期13卷 376-386页

作者： Issei Ogasawara Ken Ohta Gajanan S.Revankar Shoji Konda Yohei Shimokochi Hideyuki Koga Ken Nakata department of Health and Sport Sciences Graduate School of MedicineOsaka UniversityToyonaka 560-0043Japan Sports Sensing Co. LTD.Fukuoka 815-0035Japan department of Neurology Graduate School of MedicineOsaka UniversitySuita 565-0871Japan department of Health and Sport Management Osaka University of Health and Sport SciencesSennan-gun 590-0496Japan department of Joint Surgery and Sports Medicine Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityBunkyo-ku 113-8519Japan

Background:Combined knee valgus and tibial internal rotation(VL+IR)moments have been shown to stress the anterior cruciate ligament(ACL)in several in vitro cadaveric studies.To utilize this knowledge for non-contact ACL injury prevention in sports,it is necessary to elucidate how the ground reaction force(GRF)acting point(center of pressure(CoP))in the stance foot produces combined knee VL+IR moments in risky maneuvers,such as cuttings.However,the effects of the GRF acting point on the development of the combined knee VL+IR moment in cutting are still unknown.Methods:We first established the deterministic mechanical condition that the CoP position relative to the tibial rotational axis differentiates the GRF vector’s directional probability for developing the combined knee VL+IR moment,and theoretically predicted that when the CoP is posterior to the tibial rotational axis,the GRF vector is more likely to produce the combined knee VL+IR moment than when the CoP is anterior to the tibial rotational axis.Then,we tested a stochastic aspect of our theory in a lab-controlled in vivo experiment.Fourteen females performed 60˚cutting under forefoot/rearfoot strike conditions(10 trials each).The positions of lower limb markers and GRF data were measured,and the knee moment due to GRF vector was calculated.The trials were divided into anterior-and posterior-CoP groups depending on the CoP position relative to the tibial rotational axis at each 10 ms interval from 0 to 100 ms after foot strike,and the occurrence rate of the combined knee VL+IR moment was compared between trial groups.Results:The posterior-CoP group showed significantly higher occurrence rates of the combined knee VL+IR moment(maximum of 82.8%)at every time point than those of the anterior-CoP trials,as theoretically predicted by the deterministic mechanical condition.Conclusion:The rearfoot strikes inducing the posterior CoP should be avoided to reduce the risk of non-contact ACL injury associated with the combined knee VL+IR stress.

关键词： center of pressure Deterministic condition Foot strike pattern Injury mechanism Moment of ground reaction force

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